Psychiatric disorders are the leading source of disability worldwide and affect 53% of the U.S. population. In addition to the individual suffering they entail, the disability associated with these disorders includes substantial consequences for family and health outcomes. This includes long-term consequences for family formation and dissolution behaviors. Dissecting the relationship among community, family and psychiatric factors is complex because of the high potential for reciprocal causation. The result is a formidable challenge to understanding the role of psychiatric disorders in a wide range of adverse outcomes. The first step toward disentangling this complex relationship is to identify the role of causal factors that precede the onset of psychiatric disorders so that subsequent steps can estimate the mediating power of psychiatric disorders in long-term outcomes. Successful documentation of these causal pathways requires the availability of longitudinal research in large cohorts with repeated measures of environmental exposures, assessment of social and family variables, genetic data, and mental health outcomes. The research we propose will address these challenges by capitalizing on one of the few such cohorts available worldwide. Here we propose to use an innovative approach, validated and initiated with NIH R56, support to significantly advance the study of mental health. This project will capitalize on a confluence of unprecedented opportunities to advance our understanding of the formation of psychiatric disorders. We propose to integrate: (1) a 20-year panel study with exceptional measurement of social environment and detailed migration histories (the CVFS); (2) a setting of unusually high exposures to risk factors (South Asia); and (3) recent advances in psychiatric genetics that have identified polygenic risk profiles contributing to psychiatric disorders. We focus on three psychiatric phenotypes that are common and have the best established relationship to social environment and family: major depressive disorder, post-traumatic stress disorder, and alcohol use disorders. Our specific aims are: 1) Create a unique scientific resource by collecting psychiatric phenotypes, demographic information and biospecimens from participants in the CVFS. The CVFS is an existing study comprising 10,000 individuals from 2,700 households in various sub-population groups; 2) Conduct demographic analyses to identify key predictors of psychiatric disorder in a large population-based sample of South Asian families and communities in a controlled- comparison design; 3) Perform genome wide genotyping and analyses to examine the role of polygenic risk scores and genetic modifiers of environmental risk and resilience factors. The project will: A) Extend both the demography of mental health and psychiatric genetic findings from the European Diaspora to South Asian populations; B) Establish the role of community and gene-environment interactions in producing common psychiatric disorders most likely to shape long-term outcomes; and C) Create a transformative new scientific resource to learn the potential of psychiatric disorders to shape many different later life outcomes.